Hospital admissions caused by adverse drug events: an Australian prospective study.

OBJECTIVE: To assess the frequency of adverse drug event (ADE)-related admissions (ADE-RAs) during a prospective medical record review of patients admitted to a metropolitan tertiary referral hospital. METHODS: Potential ADE-RA cases were identified by examination of case records of randomly selected patients. Cases were assessed by an expert panel to measure study outcomes, which were the frequency (ADEs and ADE-RAs) as well as type, likelihood of causality, severity, avoidability and detection of ADEs. RESULTS: Of the 370 subjects, 59 (16.0%) had a confirmed ADE-RA, with 15 (4.1%) of these serious and preventable. The 59 ADE-RAs were a result of 72 discreet ADEs. Adverse drug reactions were the most common type of ADE, followed by non-compliance. Of the 72 discreet ADEs, 31.9% were classified as 'probable' or 'highly probable'. Most ADEs (54.2%) were classified as 'definitely avoidable', 34.7% were classified as 'severe' and 21.8% were classified as both 'definitely avoidable' and 'severe'. Half the ADEs were detected after the patient had been admitted and most were detected by medical practitioners. Antineoplastics followed by antidiabetic agents were most frequently implicated. CONCLUSIONS: Implementing a systems approach that involves multiple strategies, such as improving tertiary-to-primary care information transfer and promoting medication adherence through education programs, is necessary to tackle the problem of avoidable ADE-RAs and the associated cost burden. WHAT IS KNOWN ABOUT THE TOPIC? It is estimated that 2-3% of Australian hospital admissions are due to adverse drug events (ADEs), but recent data are lacking. According to the Australian Statistics on Medicines, over 250 million prescriptions were dispensed in 2007, compared with just under 180 million in 1997. This 40% increase in drug utilisation over the 10 years surpasses the Australian population growth of 14% in the same period. An increase in drug use per person indicates that the rate of ADEs and possible ADE-related admissions (ADE-RAs) is likely to have increased. WHAT DOES THIS PAPER ADD? This prospective study was conducted at a large Australian metropolitan teaching hospital and we report that 59 of 370 participants (16.0%) presenting to the Emergency Department had a confirmed ADE-RA, with 15 (4.1%) presenting with a serious and preventable ADE-RA. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? The findings of this study support implementing a systems approach involving multiple strategies to tackle the problem of avoidable ADE-RAs and the associated cost burden. This study reveals that half the ADEs were not detected until after the admission process, which reinforces the importance of focusing efforts towards preventing ADE-RAs and detecting ADE-RAs through measures such as those recommended in the Australian Pharmaceutical Advisory Council guiding principles.

Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism.

Gastrointestinal disturbance is frequently reported for individuals with autism. We used quantitative real-time PCR analysis to quantify fecal bacteria that could influence gastrointestinal health in children with and without autism. Lower relative abundances of Bifidobacteria species and the mucolytic bacterium Akkermansia muciniphila were found in children with autism, the latter suggesting mucus barrier changes.

A review of candidate urinary biomarkers for autism spectrum disorder.

CONTEXT: Autism is a complex, heterogeneous neurodevelopmental condition with a strong genetic component potentially impacted by various environmental factors influencing susceptibility. There are no reliable laboratory tests available to confirm an autism diagnosis. OBJECTIVE: To examine the published literature and identify putative urinary biomarkers of autism. METHODS: A comprehensive literature search was conducted using electronic bibliographic databases. RESULTS: Putative autism biomarkers were identified that could be categorized according to the key theories that exist regarding the etiology of autism: gastrointestinal factors, immune dysregulation, heavy metal toxicity, neurotransmitter abnormalities, and oxidative stress. CONCLUSION: There is scope for specific urinary biomarkers to be useful for identification of autistic metabolic phenotypes.

Clinical outcomes of a collaborative, home-based postdischarge warfarin management service.

BACKGROUND: Warfarin remains a high-risk drug for adverse events, especially following discharge from the hospital. New approaches are needed to minimize the potential for adverse outcomes during this period. OBJECTIVE: To evaluate the clinical outcomes of a collaborative, home-based postdischarge warfarin management service adapted from the Australian Home Medicines Review (HMR) program. METHODS: In a prospective, nonrandomized controlled cohort study, patients discharged from the hospital and newly initiated on or continuing warfarin therapy received either usual care (UC) or a postdischarge service (PDS) of 2 or 3 home visits by a trained, HMR-accredited pharmacist in their first 8 to 10 days postdischarge. The PDS involved point-of-care international normalized ratio (INR) monitoring, warfarin education, and an HMR, in collaboration with the patient's general practitioner and community pharmacist. The primary outcome measure was the combined incidence of major and minor hemorrhagic events in the 90 days postdischarge. Secondary outcome measures included the incidences of thrombotic events, combined hemorrhagic and thombotic events, unplanned and warfarin-related hospital readmissions, death, INR control, and persistence with therapy at 8 and 90 days postdischarge. RESULTS: The PDS (n=129) was associated with statistically significantly decreased rates of combined major and minor hemorrhagic events to day 90 (5.3% vs 14.7%; p=0.03) and day 8 (0.9% vs 7.2%; p=0.01) compared with UC (n=139). The rate of combined hemorrhagic and thrombotic events to day 90 also decreased (6.4% vs 19.0%; p=0.008) and persistence with warfarin therapy improved (95.4% vs 83.6%; p=0.004). No significant differences in readmission and death rates or INR control were demonstrated. CONCLUSIONS: This study demonstrated the ability of appropriately trained accredited pharmacists working within the Australian HMR framework to reduce adverse events and improve persistence in patients taking warfarin following hospital discharge. Widespread implementation of such a service has the potential to enhance medication safety along the continuum of care.

Simplifying Medication Regimens for People Receiving Community-Based Home Care Services: Outcomes of a Non-Randomized Pilot and Feasibility Study.

PURPOSE: Being able to manage a complex medication regimen is key to older people continuing to live at home. This study determined the feasibility of a multi-component intervention to simplify medication regimens for people receiving community-based home care services. PATIENTS AND METHODS: Research nurses recruited people receiving community-based home care services to participate in this non-randomized pilot and feasibility study (Australian New Zealand Clinical Trials Registry ACTRN12618001130257). Participants received a one-off clinical pharmacist intervention comprising medication reconciliation, assessment of capacity to self-manage medications, and application of a structured 5-step tool to identify medication simplification opportunities. A mixed-methods feasibility assessment with an explanatory design was undertaken to assess recruitment, protocol adherence and stakeholder acceptability. Data from interviews with 12 stakeholders were thematically analyzed. Secondary outcome measures, including medication discrepancies, and changes in number of medication administration times per day, quality of life, medication adherence and health service utilization, were determined over a 4-month follow-up. RESULTS: Twenty-five out of the target 50 participants were recruited. Initial recruitment was impacted by apparent uncertain role responsibilities in medication management, with some clients who declined to participate perceiving they would be unlikely to benefit or being reluctant to change regimens. However, with few exceptions, participants who received intervention did so with a high degree of protocol adherence and acceptability. Stakeholders valued the intervention and supported wider implementation. Discrepancies between the baseline medication history from the general medical practitioner and the pharmacist-compiled "best possible medication history" were identified for all participants' regimens (median of 6 per participant), with one-third resolved at follow-up. Simplification was possible for 14 participants (56%) and implemented for 7 (50%) at follow-up. No significant changes in other secondary outcomes were observed. CONCLUSION: The intervention was delivered as planned, and valued by stakeholders. Recruitment barriers should be addressed before wider implementation.

Is urinary indolyl-3-acryloylglycine a biomarker for autism with gastrointestinal symptoms?

An autism spectrum disorder (ASD) diagnosis is based on clinical behaviours as there are no validated biological diagnostic tools. Indolyl-3-acryloylglycine (IAG) is a chemical produced by gut microflora and there are conflicting reports as to whether urinary levels are elevated in children with ASD compared with controls. Urinary IAG levels in morning urine samples were statistically significantly higher in children with ASD whose caregivers reported the presence of chronic gastrointestinal (GI) disturbance than children with ASD without chronic GI disturbance. Urinary IAG, however, was not statistically significantly higher in children with ASD, compared with siblings or unrelated controls without ASD.

The effect on medication errors of pharmacists charting medication in an emergency department.

OBJECTIVE: To determine the frequency and clinical significance of medication errors when (a) pharmacists elicit medication histories in the Emergency Department after medications have been prescribed by doctors and (b) pharmacists obtain and chart medication histories prior to doctors' approval. SETTING: The Queen Elizabeth Hospital, a 350 bed South Australian teaching hospital, serving the local adult community. METHOD: Emergency Department patients at risk of medication misadventure were recruited in two phases with a 'usual practice' arm (6 weeks) and a 'pharmacist medication charting' arm (5 weeks) reflecting an alternative intervention. In the 'usual care' arm, medication histories were compiled by a pharmacy researcher after a doctor had completed the medication chart. The researcher-elicited medication histories were compared with the doctors' medication charts and unintentional discrepancies were recorded. In the 'pharmacist medication charting' arm, the same process was followed except the researcher compiled the patients' medication histories at triage, prior to patients seeing a doctor. The medication history was then transcribed onto a medication chart for authorisation by a doctor. In addition, whether resolution of unintentional discrepancies for patients in the 'usual care' arm had occurred by discharge was determined by examining patients' medical records. Main outcome measure Frequency of unintentional discrepancies and medication errors. RESULTS: The study included 45 and 29 patients in the 'usual care' and intervention arms, respectively. In the 'usual care' arm, 75.6% of patients had one or more unintentional discrepancies compared with 3.3% in the 'pharmacist medication charting' arm. This resulted in an average of 2.35 missed doses per patient in the 'usual care' arm and 0.24 in the intervention arm. In addition, an average of 1.04 incorrect doses per patient were administered in the 'usual care' arm and none in the 'pharmacist medication charting' arm. The differences observed between the arms were statistically significant (P < 0.05) and deemed clinically significant by a multidisciplinary panel. CONCLUSION: This study provides evidence for pharmacists eliciting medication histories to prepare medication charts at the earliest possible opportunity following a patient's presentation to the Emergency Department.

The relationship between sensory processing patterns and behavioural responsiveness in autistic disorder: a pilot study.

Sensory processing (SP) difficulties have been reported in as many as 95% of children with autism, however, empirical research examining the existence of specific patterns of SP difficulties within this population is scarce. Furthermore, little attention has been given to examining the relationship between SP and either the core symptoms or secondary manifestations of autism. In the current study, SP patterns in children with autistic disorder (AD) were investigated via a caregiver questionnaire and findings were correlated with the social, emotional and behavioural responsiveness of participants. Results indicated the presence of specific SP patterns in this sample of children with AD and several significant relationships were found between SP and social, emotional and behavioural function.

Lack of evidence for genomic instability in autistic children as measured by the cytokinesis-block micronucleus cytome assay.

Autism spectrum disorders are a set of neurodevelopmental disorders that are highly hereditable. Increased genomic instability has been observed in other heritable paediatric neurobiological disorders; therefore, the aim of our study was to test the hypothesis that DNA damage is increased in children with autism and that B vitamin status may explain variations in genome integrity between autistic and normal children. We compared 35 children with autism, 27 of their siblings without autism and 25 age- and gender-matched community controls for genomic stability using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay, B vitamins and homocysteine, as well as autism-related behaviours. It was found that there were no differences in CBMN-cyt biomarkers between the three groups. Vitamin B2 was significantly raised in children with autism and their siblings compared with controls (P = 0.027 and P = 0.016 respectively) but there was no difference in other B vitamins or homocysteine. In conclusion, although replication using a larger cohort is needed, it appears unlikely that genomic instability is a feature of the aetiology of autism. We cannot rule out in utero effects or other types of DNA damage not measured by the CBMN-cyt assay.

Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder.

BACKGROUND: A recent report indicated that numbers of Sutterella spp. are elevated in gastrointestinal biopsies taken from children with autism spectrum disorder (ASD). We have recently reported changes in the numbers of some bacteria within the stool of ASD children, and now examine whether numbers of Sutterella spp. and some other mucosa-associated bacteria linked with gastrointestinal disease (Ruminococcus gnavus and Ruminococcus torques) are also altered in the stool of these children. FINDINGS: We show that numbers of Sutterella spp. are elevated in feces of ASD children relative to controls, and that numbers of R. torques are higher in the children with ASD with a reported functional gastrointestinal disorder than those without such a disorder. CONCLUSIONS: We show further evidence of changes in the gut microbiota of children with ASD and confirm that the abundance of Sutterella spp. is altered in stool.

The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis.

BACKGROUND: Glutathione has a wide range of functions; it is an endogenous anti-oxidant and plays a key role in the maintenance of intracellular redox balance and detoxification of xenobiotics. Several studies have indicated that children with autism spectrum disorders may have altered glutathione metabolism which could play a key role in the condition. METHODS: A systematic literature review and meta-analysis was conducted of studies examining metabolites, interventions and/or genes of the glutathione metabolism pathways i.e. the γ-glutamyl cycle and trans-sulphuration pathway in autism spectrum disorders. RESULTS: Thirty nine studies were included in the review comprising an in vitro study, thirty two metabolite and/or co-factor studies, six intervention studies and six studies with genetic data as well as eight studies examining enzyme activity. CONCLUSIONS: The review found evidence for the involvement of the γ-glutamyl cycle and trans-sulphuration pathway in autistic disorder is sufficiently consistent, particularly with respect to the glutathione redox ratio, to warrant further investigation to determine the significance in relation to clinical outcomes. Large, well designed intervention studies that link metabolites, cofactors and genes of the γ-glutamyl cycle and trans-sulphuration pathway with objective behavioural outcomes in children with autism spectrum disorders are required. Future risk factor analysis should include consideration of multiple nutritional status and metabolite biomarkers of pathways linked with the γ-glutamyl cycle and the interaction of genotype in relation to these factors.

Consumers' views of pharmacogenetics--A qualitative study.

BACKGROUND: Adverse drug reactions are recognized as a significant public health issue. Pharmacogenetics (PGx) provides a potential means of preventing some adverse drug reactions by predicting the optimal medication dose for an individual; however, PGx is rarely used in clinical practice. Thus far, there have been few studies investigating consumers' perceptions of the barriers to the implementation of PGx in clinical practice. OBJECTIVES: This study explored the views of the general public regarding their current use of medications, and their experiences of side effects and opinions on PGx. METHODS: Members of the general public who suffered a chronic medical condition and/or had an immediate family member with a chronic medical condition were recruited to form 5 separate focus groups (n=35). Three separate age ranges were used in the focus groups. A questioning route was developed and used in focus groups to determine participants' experiences with medication use and opinions on PGx (referred to as "Personalized Medicine"). Focus group discussions were transcribed by 2 separate investigators, and qualitative analysis, based on the framework approach, was applied to the data. Data were independently coded to identify key themes then compared both within and between focus groups. RESULTS: A common theme was a desire to have a holistic approach to disease diagnosis and medication selection. A wide range of views were expressed by the focus group participants. Concerns were raised regarding the current level of side effects experienced with medications. Storage and privacy of genetic information, and the costs involved, were also seen as potential barriers to implementation of PGx. CONCLUSIONS: PGx testing was seen as a potential positive contribution, but only if other factors were considered during the prescribing process. As participants desired a high level of information and effective communication from their health-care professionals, PGx education of clinicians and pharmacists will be essential to satisfy consumers' requirements.

Sensory processing subtypes in autism: association with adaptive behavior.

Children with autism are frequently observed to experience difficulties in sensory processing. This study examined specific patterns of sensory processing in 54 children with autistic disorder and their association with adaptive behavior. Model-based cluster analysis revealed three distinct sensory processing subtypes in autism. These subtypes were differentiated by taste and smell sensitivity and movement-related sensory behavior. Further, sensory processing subtypes predicted communication competence and maladaptive behavior. The findings of this study lay the foundation for the generation of more specific hypotheses regarding the mechanisms of sensory processing dysfunction in autism, and support the continued use of sensory-based interventions in the remediation of communication and behavioral difficulties in autism.

Folate and methionine metabolism in autism: a systematic review.

BACKGROUND: Autism is a complex neurodevelopmental disorder that is increasingly being recognized as a public health issue. Recent evidence has emerged that children with autism may have altered folate or methionine metabolism, which suggests the folate-methionine cycle may play a key role in the etiology of autism. OBJECTIVE: The objective was to conduct a systematic review to examine the evidence for the involvement of alterations in folate-methionine metabolism in the etiology of autism. DESIGN: A systematic literature review was conducted of studies reporting data for metabolites, interventions, or genes of the folate-methionine pathway in autism. Eighteen studies met the inclusion criteria, 17 of which provided data on metabolites, 5 on interventions, and 6 on genes and their related polymorphisms. RESULTS: The findings of the review were conflicting. The variance in results can be attributed to heterogeneity between subjects with autism, sampling issues, and the wide range of analytic techniques used. Most genetic studies were inadequately powered to provide more than an indication of likely genetic relations. CONCLUSIONS: The review concluded that further research is required with appropriately standardized and adequately powered study designs before any definitive conclusions can be made about the role for a dysfunctional folate-methionine pathway in the etiology of autism. There is also a need to determine whether functional benefits occur when correcting apparent deficits in folate-methionine metabolism in children with autism.

Is there a role for routinely screening children with autism spectrum disorder for creatine deficiency syndrome?

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that presents in the first three years of life. Currently, diagnosis of ASD is based on its behavioural manifestations, as laboratory diagnostic tests do not exist. Creatine deficiency syndrome (CDS) is one form of inborn error of metabolism where affected individuals have similar clinical features to individuals with ASD. Abnormal urinary creatine (CR) and guanidinoacetate (GAA) levels have been reported as biomarkers of CDS. We hypothesized that screening for abnormal levels of urinary CR and GAA in children with ASD may assist in identifying a subgroup of ASD individuals who can be managed with dietary interventions. Morning urine samples were collected from children with and without autism and analyzed for CR and GAA levels. Results showed there was no statistically significant difference in urinary CR:creatinine and GAA:creatinine between the children with ASD and sibling or unrelated controls. In conclusion, routine screening for abnormal urinary CR and GAA could be considered in ASD diagnostic protocols; however, individuals positive for CDS are likely to be rare in an ASD cohort.